Much work has been done in recent years to develop 3-dimensional (3D) engineered cardiac tissues from multiple sources, primarily from isolated rat cardiomyocytes and human embryonic stem cell-derived cardiac cells, and now induced-pluripotent stem cell sources. These engineered tissues have been generated in a number of forms for a variety of purposes such as developing a patch for damaged heart tissue in patients with myocardial infarction (MI), as well as for serving as an in-vitro testing platform for screening potential therapeutic agents, testing for toxicity, and as a replacement of animal models for studying healthy and diseased tissue.
A popular manifestation of this latter aim is the creation of engineered tissue strips that have electrical and contractile activity. The force generated by these strips has been measured through various techniques and provides functional performance characteristics of the tissue. Some of these force measurement methods include a polydimethylsiloxane (PDMS) cantilever platform with optical tracking of post deflections, as well as the standard muscle bath force testing setups using several transducer technologies (Turnbull, et al., 2013). In the former, a small PDMS cast is made with two flexible posts separated at distance of ˜1 cm, between which a fibrin/collagen/Matrigel-based 3D engineered tissue strip is grown. After some time in culture, the tissue will generate contractile force that causes the posts to bend. A video platform to optically track the displacement of the ends of the post due to bending enables the tissue-generated contractile force to be estimated non-invasively and in real-time using the bending equation for a cantilever beam.
These systems have a number of differences from muscle bath systems which have been used for decades to measure isolated cardiac and skeletal muscle tissue strips. One is that the PDMS-measured twitch force is non-isometric, which is contrary to muscle-bath systems. This can cause the contractile performance of the tissue to be underestimated due to the fact that the maximum force generated decreases with shortening and mechanical unloading of the tissue. Additionally, the tissue cannot be adequately stretched to its optimal length, unlike standard muscle-bath setups, which also limits the maximum force generation and complicates comparison of twitch force from different tissues. These differences can be considered drawbacks for the PDMS when trying to compare data to the abundance of previous experiments on natural tissue using muscle bath systems.
Likewise, the muscle bath also has limitations, including high expense, low throughput, non-sterile environment, and tissue damage due to clamping. Thus, there are limitations to both systems and is therefore a desire to provide a bioreactor system that can overcome the above limitations and deficiencies associated with the traditional designs.